The project intended to provide a vehicle promoting interaction and collaboration in pursuit of common interests in regulatory abnormalities in immunological diseases. The program has an emphasis on investigation of regulatory subpopulations of T cells that may be relevant to pathogenesis or that may function abnormally in certain immunological diseases. It consists of seven projects each with defined and independent objectives which will amplify each other through development of related studies on physiologic and pathologic regulation of the immune system. It will also support essential core laboratory facilities for flow cytometry and tissue typing. Focus of the application is distinctly on clinical investigation, although two projects will study disease related immunological dysfunction in autoimmune mice. The investigators bring to the program clinical skills in immunology, rheumatology and infectious diseases and scientific expertise in human and murine immunogenetics, immunochemistry, cellular immunology, transplantation immunology and viral immunology. Studies will be performed primarily in vitro and both T cell-mediated and antibody-induced models of normal and pathological immunoregulatory function will be defined. Several specific diseases will be investigated. These include: AIDS, insulin-dependent diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, and immune deficiencies associated with viral infection. These diseases reflect extensions of established interests of the investigators, provide new opportunities for defining pathologic immunoregulatory processes that may have important pathogenetic consequences.